Cell Reports (Dec 2015)

Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status

  • Camilla A. Richmond,
  • Manasvi S. Shah,
  • Luke T. Deary,
  • Danny C. Trotier,
  • Horatio Thomas,
  • Dana M. Ambruzs,
  • Lijie Jiang,
  • Bristol B. Whiles,
  • Hannah D. Rickner,
  • Robert K. Montgomery,
  • Alessio Tovaglieri,
  • Diana L. Carlone,
  • David T. Breault

DOI
https://doi.org/10.1016/j.celrep.2015.11.035
Journal volume & issue
Vol. 13, no. 11
pp. 2403 – 2411

Abstract

Read online

The cellular and molecular mechanisms underlying adaptive changes to physiological stress within the intestinal epithelium remain poorly understood. Here, we show that PTEN, a negative regulator of the PI3K→AKT→mTORC1-signaling pathway, is an important regulator of dormant intestinal stem cells (d-ISCs). Acute nutrient deprivation leads to transient PTEN phosphorylation within d-ISCs and a corresponding increase in their number. This release of PTEN inhibition renders d-ISCs functionally poised to contribute to the regenerative response during re-feeding via cell-autonomous activation of the PI3K→AKT→mTORC1 pathway. Consistent with its role in mediating cell survival, PTEN is required for d-ISC maintenance at baseline, and intestines lacking PTEN have diminished regenerative capacity after irradiation. Our results highlight a PTEN-dependent mechanism for d-ISC maintenance and further demonstrate the role of d-ISCs in the intestinal response to stress.

Keywords